TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29543	88852;88853;88854	chr2:178554720;178554719;178554718	chr2:179419447;179419446;179419445
N2AB	27902	83929;83930;83931	chr2:178554720;178554719;178554718	chr2:179419447;179419446;179419445
N2A	26975	81148;81149;81150	chr2:178554720;178554719;178554718	chr2:179419447;179419446;179419445
N2B	20478	61657;61658;61659	chr2:178554720;178554719;178554718	chr2:179419447;179419446;179419445
Novex-1	20603	62032;62033;62034	chr2:178554720;178554719;178554718	chr2:179419447;179419446;179419445
Novex-2	20670	62233;62234;62235	chr2:178554720;178554719;178554718	chr2:179419447;179419446;179419445
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Fn3-103
• Domain position: 11
• Structural Position: 12
• Q(SASA): 0.2237
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
F/S	rs948542254	None	0.998	N	0.781	0.499	0.746204736577	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
F/S	rs948542254	None	0.998	N	0.781	0.499	0.746204736577	gnomAD-4.0.0	3.71806E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.08541E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
F/A	0.8895	likely_pathogenic	0.8817	pathogenic	-2.386	Highly Destabilizing	0.992	D	0.65	neutral	None	None	None	None	N
F/C	0.4738	ambiguous	0.4825	ambiguous	-1.855	Destabilizing	1.0	D	0.791	deleterious	N	0.475693604	None	None	N
F/D	0.9819	likely_pathogenic	0.98	pathogenic	-1.38	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
F/E	0.9746	likely_pathogenic	0.9697	pathogenic	-1.207	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
F/G	0.9544	likely_pathogenic	0.9522	pathogenic	-2.798	Highly Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
F/H	0.8883	likely_pathogenic	0.8638	pathogenic	-1.121	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
F/I	0.3029	likely_benign	0.3276	benign	-1.096	Destabilizing	0.978	D	0.537	neutral	N	0.40252121	None	None	N
F/K	0.9613	likely_pathogenic	0.9513	pathogenic	-1.853	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
F/L	0.9128	likely_pathogenic	0.9235	pathogenic	-1.096	Destabilizing	0.948	D	0.539	neutral	N	0.450371085	None	None	N
F/M	0.6416	likely_pathogenic	0.6566	pathogenic	-1.016	Destabilizing	0.999	D	0.64	neutral	None	None	None	None	N
F/N	0.9164	likely_pathogenic	0.9089	pathogenic	-2.134	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
F/P	0.9742	likely_pathogenic	0.9741	pathogenic	-1.527	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
F/Q	0.9504	likely_pathogenic	0.9397	pathogenic	-2.031	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
F/R	0.9445	likely_pathogenic	0.9332	pathogenic	-1.389	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
F/S	0.8809	likely_pathogenic	0.8741	pathogenic	-2.984	Highly Destabilizing	0.998	D	0.781	deleterious	N	0.507939308	None	None	N
F/T	0.869	likely_pathogenic	0.8616	pathogenic	-2.697	Highly Destabilizing	0.998	D	0.765	deleterious	None	None	None	None	N
F/V	0.3836	ambiguous	0.3843	ambiguous	-1.527	Destabilizing	0.543	D	0.364	neutral	N	0.37812141	None	None	N
F/W	0.6482	likely_pathogenic	0.6467	pathogenic	-0.126	Destabilizing	1.0	D	0.631	neutral	None	None	None	None	N
F/Y	0.2396	likely_benign	0.2188	benign	-0.501	Destabilizing	0.998	D	0.619	neutral	N	0.485563881	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.